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. 2016 Aug 24;21(9):1113.
doi: 10.3390/molecules21091113.

Efficient Synthesis of Fully Substituted Pyrrolidine-Fused 3-Spirooxindoles via 1,3-Dipolar Cycloaddition of Aziridine and 3-Ylideneoxindole

Wen Ren  1 , Qian Zhao  2 , Chuan Zheng  3 , Qiong Zhao  4 , Li Guo  5 , Wei Huang  6
Affiliations

Efficient Synthesis of Fully Substituted Pyrrolidine-Fused 3-Spirooxindoles via 1,3-Dipolar Cycloaddition of Aziridine and 3-Ylideneoxindole

Wen Ren et al. Molecules. .

Abstract

Drug-like spirocyclic scaffolds have been prepared by fusing fully functionalized pyrrolidine with oxindoles in an approach based on 1,3-dipolar cycloaddition. Reaction between aziridine and 3-ylideneoxindole generated diverse spirooxindole-pyrrolidines in good yield (up to 95%) with high diastereoselectivity (up to >20:1). The reaction also proceeded smoothly with several other synthetically useful activated trisubstituted olefins. The mild reaction conditions, short reaction times, and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting spiro-architectures.

Keywords: 1,3-dipolar cycloaddition; aziridine; single-step reaction; spirooxindole-pyrrolidine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of the spirooxindole-pyrrolidine framework in biologically active molecules.
Scheme 1
Scheme 1
1,3-Dipolar cycloaddition-based synthesis of spirooxindole-pyrrolidines.
Scheme 2
Scheme 2
Synthetic strategy.
Scheme 3
Scheme 3
Synthesis of pharmacologically important spiro-pyrrolidines.
Figure 2
Figure 2
X-ray structure of 3a.
See this image and copyright information in PMC

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